Table 2.

Cyclic changes in neural activity and cardiorespiratory forces that drives CSF flow and glymphatic activity during sleep and wakefulness

Frequency	Brain State	Cause	Physiological Driver on CSF dynamics	Effect on Ventricular CSF	Effect on Glymphatics	References
Very high: 0.8–1.2 Hz or every ∼1 s	Wakefulness and sleep	Cardiovascular cycle	Arterial pulsations	Minor low amplitude contribution compared with respiratory forces (Human)	Forward pumping of CSF in periarterial surface vessels (Mice)	(21, 54, 495, 498, 515)
High: 0.4-0.25 Hz or every ∼4 s	Wakefulness and sleep	Respiratory cycle	Venous pulsations, drop in venous blood volume and changes in ICP	Inspiration causes largest amplitude changes during wakefulness in CSF flow leading to increased inward flow from 3rd to 4th ventricle (Human)	Venous pulsations are believed to drive extracellular fluid efflux from brain*	(495, 498, 515)
Very low: 0.05 Hz or every ∼20 s	NREM stage 2 sleep	Sleep spindles or K complexes oscillations trigger vasodilation followed by vasoconstriction	Change in BOLD signal reflecting dynamic changes in vascular tone	Largest changes in intraventricular CSF flow, also relative to wakefulness Leads to increased inward flow from 3rd to 4th ventricle (Human)	A drop in arterial blood volume could lower perivascular space resistance to CSF flow and large oscillations in arterial blood volume could act as a pump*	(469, 501)
Low: 0.1 Hz or every ∼10 s	Wakefulness	Increased neural activity in the γ-band leading to vasodilation followed by vasoconstriction	Arterial constriction that follows the neural activity driven dilation	Little or no effect (Human)	Increased brain extracellular space clearance. Likely occurring by the same mechanisms as above, albeit with lower amplitude changes (Mice)	(439, 501)

ICP, intracranial pressure, CSF, cerebrospinal fluid; NREM, nonrapid eye movement; BOLD, blood oxygenation level-dependent. *Hypothesis, not experimentally proven.